Objective: Mobility limitations and falls are common in people with Parkinson’s disease (PwP). Compared with exercise alone, a tailored, multidomain intervention has the potential to be more effective in improving mobility safety and preventing falls. This study aimed to explore the feasibility and potential effectiveness of a multidomain fall prevention intervention (Integrate) designed for PwP who experience frequent falls. Methods: The home-based intervention was delivered over a span of 6 months by occupational therapists and physiotherapists. The personalized intervention included home fall hazard reduction, exercise, and safer mobility behavior training. The participants received 8 to 12 home visits and were supported by care-partners (when necessary) to participate in the intervention. Results: Twenty-nine people (recruitment rate: 49%; drop-out rate: 10%) with moderate to advanced Parkinson’s disease, a history of recurrent falls, and mild to moderate cognitive impairment participated in the study, with 26 people completing the study. A moderate-to-high adherence to the intervention was observed, and there were no adverse events related to the intervention. Twenty-one (81%) participants met or exceeded their safer mobility goal based on the Goal Attainment Scale. The participants exhibited a median 1.0-point clinically meaningful improvement according to the Short Physical Performance Battery. An exploratory analysis revealed that fall rates were reduced by almost 50% in the 6-month follow-up period (incidence rate ratio: 0.51; 95% confidence interval 0.28–0.92). Conclusion A multidomain occupational therapy and physiotherapy intervention for PwP experiencing recurrent falls was feasible and appeared to improve mobility safety. A randomized trial powered to detect the effects of the intervention on falls and mobility is warranted.

Objective: We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease. Methods: Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs. Results: During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend. Conclusion Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

Objective: Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features. Methods: All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L. Results: The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts. Conclusion We expand the literature on CSF1R-L patients from India by reporting four new cases.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Objective: The outcomes of motor and nonmotor features of Parkinson’s disease (PD) following deep brain stimulation (DBS) vary among its subtypes. We tested whether preoperative motor subtyping using the modified tremor/postural instability and gait difficulty ratio (T/P ratio) could indicate the short-term motor, nonmotor and quality of life (QOL) outcomes of subthalamic nucleus (STN) DBS. Methods: In this prospective study, 39 consecutive STN DBS patients were assessed in the drug-OFF state before surgery and subtyped according to the T/P ratio. Patients were reassessed 6 months after surgery in the stimulation ON-drug-OFF state, and the percentage changes in motor, nonmotor and QOL scores (Parkinson’s Disease Quality of Life Questionnaire [PDQ-39]) were calculated. Results: The modified T/P ratio was moderately and positively correlated with the percentage change in the Unified Parkinson’s Disease Rating Scale III score in the OFF state, the sum of cardinal motor signs, the Non-Motor Symptom Scale score, and QOL (PDQ-39). Conclusion Preoperative PD motor subtyping can be used as an indicator of the short-term outcomes of STN DBS in PD patients.